1. ¹Department of Internal Medicine, University Tor Vergata of Rome, Rome, Italy
2. ²Institute of Cell and Molecular Science, Bart's and the London School of Medicine and Dentistry, London, UK

Correspondence: TT MacDonald, (t.t.macdonald@qmul.ac.uk)

Received 23 October 2007; Accepted 4 December 2007; Published online 23 January 2008.

Abstract

In healthy individuals, antigens from the gut lumen are tolerated by the mucosal immune system. However, a loss of tolerance toward the bacterial microflora probably causes inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis. The abnormal activation of the immune system in the gut of IBD patients is characterized by a cascade of cellular events orchestrated by cytokine cross talk between immune and non-immune cells. Interleukin (IL)-21, the newest member of the common -chain-dependent cytokine family, is a key component of the inflammatory cascade in the gut. It is highly expressed in CD and sustains the ongoing T helper type 1 (Th1)-mediated immune response. IL-21 is essential for the differentiation of Th17 cells. IL-21 is also involved in recruiting T cells to the inflamed gut and eliciting the secretion of matrix-degrading enzymes by gut fibroblasts. Overall, there is now sufficient evidence to suggest that targeting IL-21 will be of therapeutic benefit in IBD.